PB1924: INCIDENCE OF CARDIOVASCULAR AND BLEEDING EVENTS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS (CLL) TREATED WITH IBRUTINIB – A RETROSPECTIVE ANALYSIS ON CONSECUTIVE PATIENTS FROM A WELL-DEFINED REGION.
Authors: Maria Andersson, Hemming Johansson, Anders Österborg, Agneta Månsson-Broberg, Lotta Hansson, Marzia Palma
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Treatment with ibrutinib, the first-in-class inhibitor of Bruton’s tyrosine kinase (BTK), is associated with cardiovascular side effects, in particular atrial fibrillation (AF) and hypertension, as well as an increased risk of bleeding events that in clinical trials have been reported in 4-16%, 4-30% and (grade 3-4) 4-10% of patients, respectively. Outside clinical trials, treatment duration with BTKis is indefinite with continuous therapy until disease progression or unacceptable toxicity occurs. Aims: To describe the incidence of cardiovascular and bleeding events in a real-world cohort of patients (pts) with CLL undergoing ibrutinib therapy. We also explored dose intensity, length of treatment and reasons for therapy withdrawal. Methods: Pts with CLL treated with ibrutinib for ≥ 1 month (mo) during the period January 2013 to September 2021 at the Department of Hematology at Karolinska University Hospital were identified. Clinical data including pre-existing cardiovascular comorbidities and occurrence of new or worsening of pre-existing cardiovascular or bleeding events were collected from medical records until last follow-up December 2022. The outcome measure was occurrence and severity of such events. Results: A total of 134 pts were identified. The median age at start of treatment was 74 years (range 22-94). The median number of prior treatments was 2 (range 0-7) and 33 (25%) pts received ibrutinib as first-line treatment. The most common cardiovascular comorbidities at baseline were: hypertension (41%), diabetes mellitus (20%) and AF (18%). At a median follow-up at 31,5 mo (range 2,5-103), the progression-free-survival rate was 62%. Median duration of treatment was 26 mo (range 1,5-103). Sixty-three (47%) pts experienced at least 1 dose reduction during treatment and the most common reason was minor bleeding events and/or an increased risk of bleeding. At the end of the study period 91 pts (68%) had discontinued treatment. The most common reason for permanent withdrawal was toxicity (24%), where infection and bleeding were the most common causes, followed by unrelated death (19%) and progressive disease (13%). Of those pts with no AF at treatment start, AF occurred in 27/110 pts (25%) after a median time of 5 mo (range 0.5-59). Their median age at AF diagnosis was 76 years (range 44-88). Six of 24 (25%) pts with pre-existing AF experienced worsened AF during ibrutinib treatment. Four pts discontinued treatment permanently due to AF; of these, 2 had no prior history of AF and 2 had AF at treatment start. In a comparison of the pts who developed AF and those who didn’t, neither age nor cardiovascular comorbidity at start of treatment were significantly different between the groups. Seventy-nine of the 134 pts had no previous history of hypertension at treatment start. Of these, 9 (11%) pts were diagnosed with hypertension during ibrutinib treatment. Of the 55 pts who had preexisting hypertension at start of treatment, 12 (22%) worsened during treatment. One pt discontinued treatment due to hypertension. Bleeding events occurred in 89 pts (66%). Of these, the majority were grade 1-2, occurring in 79 pts (59%) of which the vast majority was bruising. Grade 3/4 events occurred in 10 pts (7.5%). Eight pts discontinued treatment due to bleeding event. Summary/Conclusion: Almost one fourth of the pts in this real-world study discontinued ibrutinib permanently due to toxicity. The incidence of AF was higher than reported in clinical studies which may be explained by older age and frequent comorbidities in our real-world cohort.Keywords: Side effects, B cell chronic lymphocytic leukemia, ibrutinib